1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 22258799, compound

HRID 1611201Notes

Reaction equation

HRID 1611201 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=O)=[C:6]([CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[CH:5]=[C:4]([C:23]2[C:28]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)=[CH:27][CH:26]=[CH:25][C:24]=2[O:39][CH2:40][CH:41]2[CH2:43][CH2:42]2)[N:3]=1.CC[O:46][C:47]([CH:49](P(OCC)(OCC)=O)[F:50])=O.[Cl-].[Li+].N12CCCN=C1CCCCC2>C(#N)C>[CH:41]1([CH2:40][O:39][C:24]2[CH:25]=[CH:26][CH:27]=[C:28]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C:23]=2[C:4]2[CH:5]=[C:6]([CH:10]3[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:11]3)[C:7]3[CH:8]=[C:49]([F:50])[C:47](=[O:46])[NH:1][C:2]=3[N:3]=2)[CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium ChlorideHCID 2734865Triethyl 2-fluoro-2-phosphonoacetateHCID 22258763HCID 22258763, compound

Product 1

HCID 22258799HCID 22258799, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of tert-butyl 3-(2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-formyl-4-pyridinyl)-1-piperidinecarboxylate (0.500 g, 0.851 mmol), triethyl-2-fluoro-2-phosphonoacetate (0.350 mL, 1.701 mmol) and anhydrous lithium chloride (0.072 g, 1.701 mmol) in acetonitrile (20 mL) was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.250 mL, 1.701 mmol). The mixture was stirred at room temperature for 30 min and concentrated under reduced pressure. The residue was extracted with ethyl acetate and water. The separated organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1-1/1) to give tert-butyl 3-(2-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-6-fluoro-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl)-1-piperidinecarboxylate as a form (0.261 g, 49%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with ethyl acetate and water
  3. washThe separated organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1-1/1)

Sources & evidence

ORD record
ord-d4b543a2913d4df39fc100edd862e770
Source dataset
uspto-grants-2006_01
Patent number
US06984649B1

Reaction notes

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